Integrated proteomics reveals brain-based cerebrospinal fluid biomarkers in asymptomatic and symptomatic Alzheimer’s disease
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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- Teacher spread
- 0.297 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
Abstract
Alzheimer's disease (AD) lacks protein biomarkers reflective of its diverse underlying pathophysiology, hindering diagnostic and therapeutic advancements. Here, we used integrative proteomics to identify cerebrospinal fluid (CSF) biomarkers representing a wide spectrum of AD pathophysiology. Multiplex mass spectrometry identified ~3500 and ~12,000 proteins in AD CSF and brain, respectively. Network analysis of the brain proteome resolved 44 biologically diverse modules, 15 of which overlapped with the CSF proteome. CSF AD markers in these overlapping modules were collapsed into five protein panels representing distinct pathophysiological processes. Synaptic and metabolic panels were decreased in AD brain but increased in CSF, while glial-enriched myelination and immunity panels were increased in brain and CSF. The consistency and disease specificity of panel changes were confirmed in >500 additional CSF samples. These panels also identified biological subpopulations within asymptomatic AD. Overall, these results are a promising step toward a network-based biomarker tool for AD clinical applications.
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The record
- Venue
- Science Advances
- Topic
- Alzheimer's disease research and treatments
- Field
- Medicine
- Canadian institutions
- —
- Funders
- National Institute on AgingWeston Brain InstituteAlzheimer’s Research UKNational Institute of Neurological Disorders and StrokeAlzheimer's AssociationMichael J. Fox Foundation for Parkinson's ResearchFoundation for the National Institutes of Health
- Keywords
- Cerebrospinal fluidProteomeProteomicsBiomarkerPathophysiologyMedicineAsymptomaticMultiplexDiseaseBiomarker discoveryAlzheimer's diseaseNeurosciencePathologyBioinformaticsBiologyGene
- Has abstract in OpenAlex
- yes